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Expression and function of murine receptor tyrosine kinases, TIE and TEK,
in hematopoietic stem cells
M Yano, A Iwama, H Nishio, J Suda, G Takada and T Suda
Department of Cell Differentiation, Institute of Molecular Embryology and
Genetics (IMEG), Kumamoto University School of Medicine, Japan.
Two highly related receptor tyrosine kinases, TIE and TEK, comprise a
family of endothelial cell-specific kinase. We established monoclonal
antibodies against them and performed detailed analyses on their expression
and function in murine hematopoietic stem cells (HSCs). TIE and TEK were
expressed on 23.7% and 33.3% of lineage marker-negative, c- Kit+ and Sca-1+
(Lin- c-Kit+ Sca-1+) HSCs that contain the majority of day-12
colony-forming units-spleen (CFU-S) and long-term reconstituting cells, but
not committed progenitor cells. Lin- c-Kit+ Sca-1+ cells were further
divided by the expression of TIE and TEK. TIE+ and TEK+ HSCs as well as
each negative counterpart contained high proliferative potential
colony-forming cells and differentiated into lymphoid and myeloid progenies
both in vitro and in vivo. However, day-12 CFU-S were enriched in TIE+ and
TEK+ HSCs. Our findings define TIE and TEK as novel stem cell marker
antigens that segregate day-12 CFU-S, and provide evidence of novel
signaling pathways that are involved in the functional regulation of HSCs
at a specific stage of differentiation, particularly of day-12 CFU-S.
Volume 89,
Issue 12,
pp. 4317-4326,
06/15/1997
Copyright © 1997 by The American Society of Hematology
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